As part of an integrated effort between the Pathogenetics Unit and the Urologic Oncology Branch, CCR, we identified a large number of deregulated transcripts and proteins in human prostate cancer, including a gene set that segregates high- and moderate grade cancer, and a gene set that segregates androgen-dependent and androgen-independent disease. Efforts are continuing to better understand the molecular nature of prostate tumorigenesis, and to identify gene expression profiles associated with clinically aggressive cancer. Additionally, we discovered a new type of epigenetic methylation field in prostate cancer that may assist in understanding the pathogenesis of the tumor microenvironment. In a search for genes involved in the development of esophageal tumors, we are collaborating with the Cancer Prevention Studies Branch, CCR, to examine the molecular basis of esophageal squamous cell carcinoma (ESCC) in a high-risk population in Shanxi province in China. Allelotype comparison of patients with and without a family history of ESCC identified a region on chromosome band 13q12 that may harbor a familial tumor suppressor gene. Efforts are underway to analyze several candidate genes in the genomic region of interest. Multiple Endocrine Neoplasia Type I (MEN1) is an inherited syndrome characterized by development of neuroendocrine tumors in affected individuals. The responsible gene was discovered in 1997 by the NIH MEN1 working group, including the Pathogenetics Unit and groups from the National Human Genome Research Institute, the National Center for Biotechnology Information, and the National Institute of Diabetes and Digestive and Kidney Diseases. Current efforts of the Pathogenetics Unit include immunohistochemical evaluation of menin in human tissues.